Human herpesvirus 8 (HHV-8) is the likely causative agent of Kaposi sarcoma, and is also found in AIDS-associated Primary Effusion Lymphoma (PEL). Although the only viral proteins known to be expressed during latent HHV-8 infection are LANA and the viral cyclin D homologue, the hypervariable K1 ORF, which has been shown to have transforming activity in rodent cells, and which can substitute for the major transforming protein (STP) of the homologous herpesvirus samarai, may also play a role in HHV-8 transformation. K1 ORF is a highly glycosylated membrane protein with an ITAM motif in its cytoplasmic tail. The specific aims of this revised proposal are to 1) define the promoter regulatory elements of the K1 ORF, and determine if this gene can also be transcribed during HHV-8 latency in particular cell types; 2) define the functional importance of the ITAM motif (as well as other motifs) in the K1 ORF in various cell types, and 3) define the role of the K1 ORF in HHV-8 transformation and lytic reactivation.